Introduction to Basic Pathology; Cellular Reaction to Injuries`

1. Introduction to Basic Pathology; Cellular Reaction to Injuries` Dr. ROOPA Pathophysiology Premed 2

2. Basic Pathophysiology • Basic Pathology • Basic Microbiology Bacteriology Virology Mycology Immunology • Basic Pharmacology

3. What is Pathology?

4. Pathology • Branch of Medicine • Studies the underlying causes of diseases “etiology” • Mechanisms that result in the signs and symptoms of the patient “pathogenesis”

5. Pathology • Bridge between basic science and clinical practice • “study of suffering” • Divisions: General Pathology Systemic Pathology

6. The Cell

7. How do cells react to environmental stress? • Hypertrophy • Hyperplasia • Aplasia • Hypoplasia • Atrophy • Metaplasia

8. Hypertrophy • Increase in protein synthesis/ organelles • Increase in size of cells • Increase in organ/tissue size

9. Hypertrophy

10. Hyperplasia • Increase in NUMBER of cells • Increase in size of organ/tissue • Similar end result as hypertrophy • May occur with hypertrophy

11. Hyperplasia

12. Aplasia • Failure of cell production • Agenesis or absence of an organ:fetus • Loss of precursor cells:adults

13. Aplasia

14. Hypoplasia • Decrease in cell production

15. Atrophy • Decrease in mass of preexisting cells • Smaller tissue/organ • Most common causes: disuse poor nutrition lack of oxygen lack of endocrine stimulation aging injury of the nerves

16. Atrophy

17. Metaplasia • Replacement of one tissue by another tissue • Several forms: Squamous metaplasia Cartilaginous metaplasia osseous metaplasia myeloid metaplasia

18. Metaplasia

19. DEFINITION- DYSPLASIA • Dysplasia means disordered growth, most commonly seen in squamous epithelial cells following chronic injury.

20. What are the causes of injury/stress? • Hypoxic cell injury • Free radical injury • Chemical cell injury

21. Hypoxic cell injury • Complete lack of oxygen/ decreased oxygen • Anoxia or hypoxia • Causes: ischemia anemia carbon monoxide poisoning decrease tissue perfusion poorly-oxygenated blood

22. Hypoxic cell injury

23. Early stage Hypoxic cell injury • Decrease in production of ATP • Changes in cell membrane • Cellular swelling endoplasmic reticulum mitochondria • Ribosomes disaggregate • Failure of protein synthesis • Clumping of chromatin

24. Late stage • Cell membrane damage myelin blebs cell blebs

25. Cell Death • Irreversible damage to the cell membranes • Calcium influx • Mitochondria calcifies • Release of cellular enzymes • Most vulnerable cells: neurons

26. Free radicals: superoxide and hydroxyl radicals • Seen in: normal metabolism oxygen toxicity ionizing radiation UV light drugs/chemicals ischemia

27. Mechanisms to detoxify free radicals • Glutathione • Catalase • Superoxide dismutase • Vitamin A, C, E • Cysteine,glutathione, selenium, ceruloplasmin • Spontaneous decay

28. Chemical Injury • Carbon tetrachloride and liver damage

29. NECROSIS AND APOPTOSIS • Necrosis sum of the morphologic changes that follow cellular death in the tissue or organs. Mainly 2 processes cause the morphologic changes of necrosis; Denaturation of proteins Enzymatic digestion of organelles n other cytosolic components.

30. Autolysis – cell digestion due to hydralytic enzymes derived from dead cells. • Heterolysis ; derived from invading inflammatory cells.

31. Types of necrosis • Coagulative necrosis • Liquefactive necrosis • Caseous necrosis • Gangrenous necrosis • Fibrinoid necrosis • Fat necrosis

32. Coagulative necrosis • Interruption of the blood supply • Commonest form of necrosis • Poor collateral circulation heart kidney • Characteristic nuclear changes pyknosis karyorrhexis karyolysis disappearance of a nuclei

33. NUCLEAR CHANGES • Karyolysis- disintegration and dissolution of a cell nucleus when a cell dies • Due to DNA se activity • Basophilia of chromatin fade

34. NUCLEAR CHANGES • Pyknosis – a degenerative state of the cell nucleus • -Nuclear shrinkage • - Increased basophilia • Karyorrhexis – nuclear fragmentation • within 1 or 2 days nucleus disappears.

35. Coagulative Necrosis

36. Liquefactive necrosis • Is typically found in the brain or in an abscess. Tissue is softened through the action of enzymes released from brain or in the case of an abscess, PMN.

37. Liquefactive necrosis

38. Caseous necrosis • Coagulative + liquefactive • “cheese - like” • Part of granulomatous inflammation • Classic picture: Tuberculosis

39. Caseous necrosis

40. Gangrenous necrosis • Interuption of the blood supply to the lower extremities or bowels • Wet type: complicated by liquefactive necrosis • Dry type: complicated by coagulative necrosis

41. Gangrenous necrosis

42. Fibrinoid necrosis • Immune-mediated vascular damage • Protein – like material in the blood vessel walls

43. Fat necrosis • Traumatic fat necrosis – after injury Breast • Enzymatic fat necrosis – after inflammation Pancreas

44. FAT NECROSIS

45. APOPTOSIS -”Programmed cell death” • Occurs when a cell dies through the activation of an internal suicide program. • This is mainly useful in eliminating the unwanted cells with minimal disruption of the surronunding tissue. • Can be seen mainly in the elimination of unwanted cells during embryogenesis.

46. Gross irreversible cell injury Passive form of cell death Does not require genes, protein synthesis Marked inflammatory reaction Physiologic programmed cell removal Active form of cell death Requires genes, proteins, energy No inflammatory reaction Necrosis versus apoptosis

47. Genes affecting apoptosis • Inhibits: bcl-2 • Facilitates: bax p53

48. Morphological features in apoptosis • Involves small clusters of cells only • No inflammatory cells • Cell membrane blebs • Cytoplasmic shrinkage • Chromatin condensation • Phagocytosis of apoptotic bodies